title: TAB2, an important upstream adaptor of interleukin-1 signaling pathway, is subject to SUMOylation.
abstract: SUMOylation has been considered as an important mechanism to regulate multiple cellular processes, including inflammation. TAB2 (TAK1-binding protein 2) is an upstream adaptor protein in the IL-1 signaling pathway. Covalent modifications of TAB2 have not been well studied. In this study, we demonstrated that TAB2 could be modified by SUMO. Using Ubc9 (SUMO-conjugating enzyme) fusion and mutation analysis, we identified evolutionarily conserved lysine 329 as the major SUMOylation site of TAB2. PIAS3, a SUMO E3 ligase, preferentially interacted with and promoted its SUMOylation. Interestingly, block of SUMOylation by mutation of lysine 329 enhanced the activity of TAB2, as reflected by AP-1 luciferase reporter assays. Taken together, these results suggest that SUMOylation may serve as a novel mechanism for the regulation of TAB2.
authors.affiliation: Shanghai Clinical Center for Endocrine and Metabolic Diseases, Shanghai Institute of Endocrinology and Metabolism, School of Medicine, Ruijin Hospital, Shanghai Jiao Tong University, Shanghai, 200025, China, visit-12345@hotmail.com.
authors.forename: Xiaolin
authors.initials: X
authors.lastname: Wang
authors.forename: Jingjing
authors.initials: J
authors.lastname: Jiang
authors.forename: Yan
authors.initials: Y
authors.lastname: Lu
authors.forename: Guojun
authors.initials: G
authors.lastname: Shi
authors.forename: Ruixin
authors.initials: R
authors.lastname: Liu
authors.forename: Yanan
authors.initials: Y
authors.lastname: Cao
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000737:chemistry / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D057809:HEK293 Cells; D006801:Humans; D007375:Interleukin-1 / Q000378:metabolism*; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D008239:Lysine / Q000378:metabolism; D051379:Mice; D018832:Molecular Chaperones / Q000378:metabolism; D008969:Molecular Sequence Data; D011485:Protein Binding; D050828:Protein Inhibitors of Activated STAT / Q000378:metabolism; D015398:Signal Transduction; D058207:Sumoylation
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D007375:Interleukin-1; D018832:Molecular Chaperones; C484745:PIAS3 protein, human; D050828:Protein Inhibitors of Activated STAT; C410585:TAB2 protein, human; D048031:JNK Mitogen-Activated Protein Kinases; D008239:Lysine